Copolymerization is a well-established strategy to produce new materials from one or more monomers, with tailored properties for specific applications. Copolymerization is commonly used to prepare homochain copolymers with carbon-carbon main chains, and heterochain copolymers with carbon and other types of atoms in the polymer backbone or main chain. The sequence distribution of these copolymers can be random and non-random. For heterochain copolymers, the non-random chains may comprise block copolymers, i.e. blocks with a high number of covalently bonded repeat units of the same chemical composition; segment copolymers, i.e. segments with a small number of repeat units; or graft copolymers, i.e. side-chain grafts with a variable number of repeat units of at least one of the constituents. For homochain polymers, the non-random parts of the chains commonly comprise block and graft copolymers. These copolymers were developed over forty years ago as the A-B-A and A-B types of homochain block copolymers comprising polydiene and polystyrene long sequences as the A and B blocks, respectively. The polydiene and polystyrene block copolymers having no functional pendant group have been commercialized as thermoplastic elastomers with the combined properties of elastomers that exhibit elasticity at room temperature, and thermoplastics with their melt processability attributes. The unique properties of these copolymers have been covered in a number of reviews, such as S. W. Shalaby and H. E. Bair, Chapter 4 in Thermal Characterization of Block Copolymers and Polyblends, E. A. Turi, Ed., Academic Press, 1981. However, nothing in the prior art has been disclosed on tailoring the structure of a homochain, linear segmented or random copolyester with segmented grafts having repeat units with pendant ester groups (e.g., those derived from vinyl acetate and alkyl methacrylates) to impart certain properties for a sought biomedical application. These structures, with or without the segmented grafts, are herein referred to as segmented homochain copolyesters. Exploration of homochain polyesters has been extended to studying the formation of linear segmented homochain copolyesters and random copolymers with segmented grafts and unique properties for use as an effective metal-adhering barrier coating, with or without a bioactive agent, for blood-contacting biomedical implanted devices.
The efficacity of endovascular stents may be increased by the addition of stent coatings that contain pharmaceutical drugs. These drugs may be released from the coating while in the body, delivering their patent effects at the site where they are needed. The localized levels of the medications may be high, and therefore potentially more effective than orally or intravenously delivered drugs that distribute throughout the body, and which may have little effect on the impacted area, or may be expelled rapidly from the body without reaching their pharmaceutical intent. Furthermore, drug release from tailored stent coatings may have controlled, timed-release qualities, eluting their bioactive agents over hours, weeks or even months.
A composition with a bioactive agent for coating the surface of a medical device based on poly (alkyl)(meth)acrylate and poly(ethylene-co-vinyl acetate) is described in “Bioactive Agent Release Coating,” Chudzik, et al., U.S. Pat. No. 6,214,901, issued Apr. 10, 2001. A composite polymer coating with a bioactive agent and a barrier coating formed in situ by a low energy plasma polymerization of a monomer gas is described in “Polymeric Coatings with Controlled Delivery of Active Agents,” K. R. Kamath, publication WO 00/32255, published 8 Jun. 2000. A polymeric coating for an implantable medical article based on hydrophobic methacrylate and acrylate monomers, a functional monomer having pendant chemically reactive amino groups capable of forming covalent bonds with biologically active compounds, and a hydrophilic monomer wherein a biomolecule is coupled to the coated surface, is presented in “Implantable Medical Device,” E. Koulik, et al., U.S. Pat. No. 6,270,788, issued Aug. 7, 2001. Use of block copolymers on a hydrophobic polymer substrate is described in “Biocompatible Polymer Articles,” E. Ruckenstein, et al., U.S. Pat. No. 4,929,510, issued May 29, 1990. A method for the columetic inclusion and grafting of hydrophilic compounds in a hydrophobic substrate using an irradiation means is described in “Hydrophobic Substrate with Grafted Hydrophilic Inclusions,” G. Gaussens, et al., U.S. Pat. No. 4,196,065, issued Apr. 1, 1980.
Unfortunately, drug polymers may not provide the mechanical flexibility necessary to be effectively used on a stent. The stent may be deployed by self-expansion or balloon expansion, accompanied by a high level of bending at portions of the stent framework, causing cracking, flaking, peeling, or delaminating of many candidate drug polymers while the stent diameter is increased by threefold or more during expansion. The candidate drug polymer may not stick or adhere, or may elute its pharmacologically active constituents too quickly or too slowly, or possibly in a toxic manner. One drug may elute much faster than a second drug in the same drug polymer, making the controlled delivery of a single drug or multiple drugs difficult. If a drug is eluted too quickly, it may be ineffective and possibly toxic. If a drug is eluted too slowly, then its intended effect on the body may be compromised. Furthermore, the coating may fall off, crystallize or melt during preparation and sterilization prior to deployment, further limiting the types of drug polymers acceptable for use on cardiovascular stents.
A drug-polymer system that can be tailored to the desired elution rate for a specific drug may be beneficial. It is desirable to have a drug-polymer system that can be tailored to accommodate a variety of drugs for controlled time delivery, while maintaining mechanical integrity during stent deployment. A polymeric system that can be readily altered to control the elution rate of an interdispersed bioactive drug and to control its bioavailability may be of further benefit.
It is an object of this invention, therefore, to provide a system for treating heart disease and other vascular conditions, to provide methods of manufacturing drug polymer coated stents, and to overcome the deficiencies and limitations described above.